The role of cyclic AMP as a mediator of adrenal function is under investigation. This role, once thought clear, has been questioned recently by studies which have failed to detect any change in intracellular cyclic AMP content in response to low doses of ACTH sufficient to stimulate steroidogenesis maximally. By correlating adrenal protein kinase activity (protein kinases are enzymes known to be under direct cyclic AMP control) with the increased corticosterone synthesis observed after graded doses of ACTH, we have attempted to clarify the role of cyclic AMP as a mediator of steroidogenesis. These studies show that ACTH can elevate steroidogenesis maximally without promoting a statistically significant increase in protein kinase activity. Based on these results we propose that cyclic AMP is a cofactor required for steroidogenesis and although cyclic AMP can stimulate steroidogenesis, the normal mediator of steroidogenesis is probably not cyclic AMP. Experiments are in progress to determine what is the normal mediator of steroidogenesis. BIBLIOGRAPHIC REFERENCES: Role of the carbohydrate of human chorionic gonadotropin in the mechanism of hormone action. W.R. Moyle, O.P. Bahl and L. Marz. J. Biol. Chem. (1975) in press. Apparent sensitive cooperativity in the mechanism of action of luteinizing hormone. D. Rodbard, W.R. Moyle and J. Ramachandran. In: Hormone Binding and Target Cell Activation of the Testis. Plenum Publishing Co., N.Y. (1974), pp. 79-87.